Population-based epidemiologic studies of communities in the United States have revealed a consistent association between ambient particulate air pollution and increases in morbidity and mortality. The observed increases result from both respiratory and cardiovascular diseases. Similar associations have been observed for rates of hospital admissions for respiratory and cardiovascular diseases for subjects over age 65. Results from the first phase of this study (ES R01 09860) showed significant cardiac and airway changes after both environmental and occupational particulate exposures. The objective of this application is to investigate the role of both occupational and non-occupational exposure to particulates in the development of respiratory and cardiac responses in boilermakers. We will employ a detailed, continuous exposure assessment to PM2.5 with and PM1.0 with repeated measures of biologic and physiologic markers of response. In addition, we will employ novel techniques for the assessment of particulate-induced physiologic responses, including gene expression using mRNA microarrays. Hypotheses to be addressed in this established cohort of boilermakers include: (1) Short-term exposure to particulates from occupational, ambient, and indoor exposures results in airway inflammation and obstruction measured by serial expired NO and FEV1; (2) Chronic exposures to particulates result in long-term decreases in expired NO and FEV1; (3) Exposure to particulates results in acute changes in cardiovascular function measured as heart-rate variability, heart-rate, and blood pressure; (4) Exposure to particulates results in increased acute phase reactant (c-reactive protein, fibrinogen) concentration in the serum; (5) Exposure to particulates induces systemic responses resulting in alterations in white blood cell gene expression assessed by mRNA microarray analysis pre- and post-exposure; (6) Common chronic medical conditions such as hypertension, COPD, and asthma predispose particulate-exposed individuals to changes in cardiac function (heart rate, heart rate variability, and blood pressure). The results of this work will have important implications for preventive efforts aimed at reducing particle-associated morbidity and mortality. [unreadable] [unreadable]